In support of the long range goals of this project, to explore the toxicological importance of aliphatic epoxides in the metabolism of alkene compounds, we will continue to study structure-mutagenicity relationships for such epoxides and attempt to develop QSAR equations to describe the mutagenicity of series of related epoxides. Compounds of interest are (a) aryl alkene oxides, b) cyclohexene oxide derivatives and their bicyclic analogues, c) aliphatic epoxide metabolites of drugs and environmental contaminants, d) methylenecyclo oxides, and e) epoxides related to fecapentaene. Mutagenicity will be measured by the plate-incorporation and liquid-preincubation procedures of the Ames test. The liquid test will also be used to study detoxification by using the Ames test in the presence of S9 liver fractions and their subfractions. These tests will be followed by HPLC for the detection of diol and glutathione detoxification products. For selective epoxides and their alkene precursors, it is planned to test the correlations and predictions gained from the Ames bacterial testing with in vivo testing using alkaline DNA unwinding assays and sister chromatid exchange as the end points. Specific-site alkylation studies of nucleosides and DNA will be extended by a comparison of N versus O alkylations as a function of SN1 or borderline SN2 versus SN2 reactions.